Nitrates are metabolised within the cell to nitric oxide. The nitric oxide activates guanylyl cyclase and produces an increase the cGMP levels in vascular smooth muscle cells. This causes a decrease in intracellular calcium levels, resulting in smooth muscle relaxation with dilatation of veins and arteries. The overall effect is of vasodilatation across the coronary circulation and a reduction in venous return, which reduces the left ventricular workload.
It is well recognised that tolerance develops but the mechanism is not understood.
- Flushing
- Headache
- Postural hypotension
- Syncope
- Acute angle glaucoma (rare)
Tachycardia can develop and is usually treated by combining nitrates and beta blockers.
Further side effects can occur if infusions are given too quickly.
Phosphodiesterase type 5 inhibitors such as Sildenafil (treatment of erectile dysfunction) are contraindicated in patients taking nitrates as this combination can cause profound hypotension.
Nitrates can increase the excretion of heparin and will reduce its effects.
Drugs which cause a dry mouth e.g. anti-muscarinics can reduce the absorption of sublingual nitrates.
No dosage adjustment is required in hepatic or renal insufficiency.
